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Gene Review

Cdx2  -  caudal type homeo box 2

Rattus norvegicus

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Disease relevance of Cdx2

  • Cdx2 staining tendency was decreased in colon tumors and adenocarcinomas compared to normal mucosa and ACF, which stained in 100% of cases [1].
  • Cdx-2 homeodomain protein expression in human and rat colorectal adenoma and carcinoma [2].
  • This report describes a study using the rat insulinoma cell line RIN-1056A, which abundantly expresses both insulin and proglucagon (glu), and relatively high amounts of endogenous Cdx-2 [3].

High impact information on Cdx2


Biological context of Cdx2

  • These data indicate that HB-EGF gene expression can be regulated by Cdx2 and serves to mediate the control of Cdx2 of the proliferation and migration of IEC-6 cells [7].
  • Reporter gene analyses showed that the HB-EGF gene promoter is Cdx2 responsive and that the activity of the promoter in the IEC-6 cells depends on the number of consensus Cdx2-binding site-like sequences [7].
  • The caudal-related homeobox transcription factor (Cdx2) plays an important role in intestinal development, differentiation, and homeostasis [6].
  • Furthermore, expression of Cdx2 in IEC-6 cells conferred the ability to express a Math1 reporter gene containing a Math1 enhancer [8].
  • Forced expression of the Cdx2 gene in undifferentiated intestinal crypt cells induces the development of a differentiated phenotype [9].

Anatomical context of Cdx2


Associations of Cdx2 with chemical compounds

  • The skeletal alterations seen in vitamin A deficiency are associated with posterior shifts in the mesodermal expression of Hoxa-4, Hoxb-3, Hoxd-3, Hoxd-4, and Hoxa-9 mRNAs, whereas the anterior domains of Hoxb-4 and Cdx2 expression are unaltered [10].
  • Cdx1 and Cdx2, known to be transcriptional factors related to intestinal proliferation and differentiation, were more highly expressed in STZ, OLETF and GK rats than in the respective controls [11].
  • Force feeding a fructose diet gave rise to an increase in the binding of the dimeric nuclear protein (Cdx-2) to the SIF1 element [12].

Other interactions of Cdx2


Analytical, diagnostic and therapeutic context of Cdx2

  • Identifying target genes regulated downstream of Cdx2 by microarray analysis [6].
  • METHODS: Nuclear protein bound to the lactase gene cis element, CE-LPH1, was analyzed by electrophoretic mobility shift assays and supershifts with Cdx2 antibody [4].
  • By immunohistochemistry with a polyclonal Cdx-2 antibody we have shown that Cdx-2 expression is markedly reduced in the later stages of human colorectal carcinogenesis, namely, high grade dysplasia and invasive carcinoma [2].


  1. Decrease in size of azoxymethane induced colon carcinoma in F344 rats by 180-day fermented miso. Ohuchi, Y., Myojin, Y., Shimamoto, F., Kashimoto, N., Kamiya, K., Watanabe, H. Oncol. Rep. (2005) [Pubmed]
  2. Cdx-2 homeodomain protein expression in human and rat colorectal adenoma and carcinoma. Ee, H.C., Erler, T., Bhathal, P.S., Young, G.P., James, R.J. Am. J. Pathol. (1995) [Pubmed]
  3. Role of Cdx-2 in insulin and proglucagon gene expression: a study using the RIN-1056A cell line with an inducible gene expression system. Zhao, Y., Liu, T., Zhang, N., Yi, F., Wang, Q., Fantus, I.G., Jin, T. J. Endocrinol. (2005) [Pubmed]
  4. The homeodomain protein Cdx2 regulates lactase gene promoter activity during enterocyte differentiation. Fang, R., Santiago, N.A., Olds, L.C., Sibley, E. Gastroenterology (2000) [Pubmed]
  5. The caudal-related homeodomain protein Cdx-2 regulates vitamin D receptor gene expression in the small intestine. Yamamoto, H., Miyamoto, K., Li, B., Taketani, Y., Kitano, M., Inoue, Y., Morita, K., Pike, J.W., Takeda, E. J. Bone Miner. Res. (1999) [Pubmed]
  6. Identifying target genes regulated downstream of Cdx2 by microarray analysis. Uesaka, T., Kageyama, N., Watanabe, H. J. Mol. Biol. (2004) [Pubmed]
  7. Heparin-binding EGF-like growth factor gene transcription regulated by Cdx2 in the intestinal epithelium. Uesaka, T., Lu, H., Katoh, O., Watanabe, H. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  8. The intestine-specific homeobox gene Cdx2 induces expression of the basic helix-loop-helix transcription factor Math1. Mutoh, H., Sakamoto, H., Hayakawa, H., Arao, Y., Satoh, K., Nokubi, M., Sugano, K. Differentiation (2006) [Pubmed]
  9. Differentiated intestinal epithelial cells exhibit increased migration through polyamines and myosin II. Rao, J.N., Li, J., Li, L., Bass, B.L., Wang, J.Y. Am. J. Physiol. (1999) [Pubmed]
  10. Vitamin A deficiency in the late gastrula stage rat embryo results in a one to two vertebral anteriorization that extends throughout the axial skeleton. Kaiser, M.E., Merrill, R.A., Stein, A.C., Breburda, E., Clagett-Dame, M. Dev. Biol. (2003) [Pubmed]
  11. Morphological changes and increased sucrase and isomaltase activity in small intestines of insulin-deficient and type 2 diabetic rats. Adachi, T., Mori, C., Sakurai, K., Shihara, N., Tsuda, K., Yasuda, K. Endocr. J. (2003) [Pubmed]
  12. Regulation of the expression of carbohydrate digestion/absorption-related genes. Goda, T. Br. J. Nutr. (2000) [Pubmed]
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